tbuckley/cabot-search huggingface dataset:
Abstract 12569: The Roles of microRNA in Preeclampsia Induced Fetal Sex-Specific Endothelial Dysfunction
Authors: Allison Yang, Savannah Senica, Tasha Pontifex, Chi Zhou
Journal: Circulation (2023)

Introduction: Preeclampsia (PE) is a hypertensive disorder that complicates 5-10% of human pregnancies and leads to high fetal morbidity and mortality. Maternal obesity increases the risks of PE by 3-fold in association with elevated circulating pro-inflammatory cytokines which are related to endothelial dysfunction observed in PE. MiR146a-5p is a cardiovascular disease-associated miRNA that regulates endothelial cell responses. We have previously reported fetal sex-specific fetal endothelial dysfunction in PE. Although miR146a-5p has been reported to be dysregulated in PE HUVECs, the role of miR146a-5p in PE-dysregulated fetal sex-specific endothelial dysfunction is unclear. Hypothesis: MiR146a-5p differently mediate PE-induced sex-specific fetal endothelial dysfunction in lean and obese pregnancies. Methods: Human umbilical vein endothelial cells (unpassaged, P0-HUVECs; 5-7 days of culture, P1-HUVECs) were isolated immediately after delivery from normotensive (NT; 39±0.5 wks) and PE (38±0.5 wks) pregnancies (lean and OB) with female (F) and male (M) fetuses. Expression of miR146a-5p was examined in P0-HUVECs using RT-qPCR (n=8-10/group). Bioinformatics analysis was performed with our existing RNAseq data to identify PE-dysregulated miR146a-5p target genes in HUVECs. Endothelial monolayer integrity (MI) responses to cytokines were examined in P1 HUVECs with and without miR146a-5p overexpression and knockdown (n=5-7/group/assay). Results: PE upregulated miR146a-5p in lean F-HUVECs, while downregulated miR146a-5p in obese M-HUVECs. PE differentially dysregulated vascular/endothelial function-associated miR146a-5p target genes (e.g., TNFα-/TGFβ-signaling pathways) in F&amp;M HUVECs. PE further reduced the TNFα-weakened MI in F and M HUVECs in both lean and OB pregnancies. TGFβ1 strengthened MI only in F-HUVECs, which was abolished in lean PE-F-HUVECs and was further decreased in OB PE-F-HUVEC. Knockdown of miR146a-5p rescues the PE-impaired MI responses to TNF-α and TGF-β1 in lean F-HUVECs but only rescues PE-impaired MI responses to TGF-β1 in OB F-HUVECs. Conclusions: MiR146a-5p plays important roles in mediating PE-induced fetal sex-specific fetal endothelial dysfunction in lean and obese pregnancies.
Abstract 15628: Digital Health Interventions for the Optimization of Postpartum Cardiovascular Health: A Systematic Review
Authors: Anais Hausvater, Mitchell Pleasure, Dorice Vieira, Darcy Banco, Dan Halpern, John A Dodson
Journal: Circulation (2023)

Introduction: Insufficient maternal care in the postpartum period (PP) has resulted in significant maternal morbidity and mortality in the U.S., most commonly due to cardiovascular (CV) disease. Digital health technologies have been proposed as a potential solution to eliminate barriers to maternal CV care. In this context we performed a systematic review to determine the benefit of digital health interventions designed to improve postpartum CV health. Methods: We conducted a systematic review of PubMed/MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Library. We included studies if the study population included PP women, and an intervention that involved digital or mobile health (including wearable devices, telemedicine, or remote monitoring). We only included studies that measured an outcome related to CV health. Two independent reviewers screened all studies and a third independent reviewer resolved any conflicts. Results: Our initial search identified 1448 studies. After removal of 143 duplicates, 1305 abstracts were screened of which 51 full studies were assessed for eligibility. Of these, 17 met inclusion/exclusion criteria. Studies were categorized into 3 broad CV outcomes: blood pressure (BP), physical activity (PA), and diet/weight loss. The majority of remote BP monitoring programs paired with telemonitoring (N=5 studies) were successful in optimizing BP, and increasing likelihood of BP measurement within 10 days PP. Interventions aimed at increasing PP physical activity included mobile applications, text-based coaching, and wearable devices such as pedometer and FitBit (N=9 studies). Just over half of these studies showed no change in PA, while the other half showed modest benefit at increasing daily or weekly PA. Weight loss interventions included smartphone applications, interactive websites, or text-based coaching (N=6 studies). Most of these studies showed a modest benefit in terms of lowered caloric intake and/or weight loss up to 1 year PP. Conclusions: The majority of studies we reviewed found that digital health interventions such as mobile health, telemonitoring and wearable devices were effective at improving postpartum CV health in the postpartum period.
Abstract 16906: Impact of ECPELLA Support on Mid-Term Survival and IABP-Shock II Score in Patients With Refractory Cardiogenic Shock Due to Acute Coronary Syndrome
Authors: Taiji Inamori, Takashi Unoki, Tomoko Nakayama, Toshiki FUKUDA, Takaaki Toyofuku, Junya Matsura, Yutaka Konami, Hiroto Suzuyama, Masayuki Inoue, Eiji Horio, Kazuhisa Kodama, Eiji Taguchi, Tadashi Sawamura, Tomohiro Sakamoto, Koichi Nakao, Jyunjiro Koyama
Journal: Circulation (2023)

Introduction: The prognosis remains extremely poor for acute coronary syndrome (ACS) with cardiogenic shock (CS) who required VA-ECMO. The IABP-SHOCK II score is a simple tool, and has demonstrated a high predictive ability for assessing the prognosis of patients with CS. Objective: To evaluate the impact of ECPELLA on intermediate-term survival compared to VA-ECMO with IABP support in patients with ACS and refractory CS and to assess the utility of the IABP-SHOCK II score in predicting outcomes for patients requiring VA-ECMO support. Methods: From January 2012 to December 2022, we enrolled 90 consecutive patients with ACS-CS who received VA-ECMO. Patents were divided into two groups; 44 patients received ECPELLA, and 46 patients received VA-ECMO with IABP. We assessed IABP-SHOCK II score and 180-day all-cause mortality. Results: There were no significant differences in age, rate of male sex, coronary risk factors, ST-elevated ACS, LMT lesion, extracorporeal cardiopulmonary resuscitation, and IABP-SHOCK II score between two groups. Kaplan-Meier analysis revealed that ECPELLA was associated with a significantly higher 180-day survival rate (p = 0.001). The patients were categorized into three groups based on the IABP-SHOCK II score: low (0-2), intermediate (3-4), and high (5-9). The IABP-SHOCK II risk score successfully stratified only the ECPELLA group into different risk categories for 30-day prognostic assessment. Conclusions: ECPELLA was associated with favorable mid-term survival compared to VA-ECMO with IABP support. Additionally, the IABP-SHOCK II score proved to be a useful tool for predicting mortality in patients treated with ECPELLA.
Microbiota in cancer: molecular mechanisms and therapeutic interventions
Authors: Zhou Chen, Defeng Guan, Zhengfeng Wang, Xin Li, Shi Dong, Junjun Huang, Wence Zhou
Journal: MedComm (2023)

Abstract The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota‐mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.
Meta-Analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy
Authors: Constantin-Cristian Topriceanu, Alexandre C. Pereira, James C. Moon, Gabriella Captur, Carolyn Y. Ho
Journal: Circulation (2023)

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted. METHODS: A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up. RESULTS: In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%–63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%–40%). Penetrance varied from ≈32% for MYL3 (myosin light chain 3) to ≈55% for MYBPC3 (myosin-binding protein C3), ≈60% for TNNT2 (troponin T2) and TNNI3 (troponin I3), and ≈65% for MYH7 (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of &lt;1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for MYBPC3 and ≈23% for MYH7 . CONCLUSIONS: The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Associations Between End-Tidal Carbon Dioxide During Pediatric Cardiopulmonary Resuscitation, Cardiopulmonary Resuscitation Quality, and Survival
Authors: Ryan W. Morgan, Ron W. Reeder, Dieter Bender, Kellimarie K. Cooper, Stuart H. Friess, Kathryn Graham, Kathleen L. Meert, Peter M. Mourani, Robert Murray, Vinay M. Nadkarni, Chandrasekhar Nataraj, Chella A. Palmer, Neeraj Srivastava, Bradley Tilford, Heather A. Wolfe, Andrew R. Yates, Robert A. Berg, Robert M. Sutton, Tageldin Ahmed, Michael J. Bell, Robert Bishop, Matthew Bochkoris, Candice Burns, Todd C. Carpenter, Joseph A. Carcillo, J. Michael Dean, J. Wesley Diddle, Myke Federman, Richard Fernandez, Ericka L Fink, Deborah Franzon, Aisha H. Frazier, Mark Hall, David A. Hehir, Christopher M. Horvat, Leanna L. Huard, Tensing Maa, Arushi Manga, Patrick S. McQuillen, Maryam Y. Naim, Daniel Notterman, Murray M. Pollack, Anil Sapru, Carleen Schneiter, Matthew P. Sharron, Sarah Tabbutt, Shirley Viteri, David Wessel, Athena F. Zuppa
Journal: Circulation (2023)

Supported by laboratory and clinical investigations of adult cardiopulmonary arrest, resuscitation guidelines recommend monitoring end-tidal carbon dioxide (ETCO
Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance
Authors: Paul M Ridker, Lei Lei, Michael J. Louie, Tariq Haddad, Stephen J. Nicholls, A. Michael Lincoff, Peter Libby, Steven E. Nissen
Journal: Circulation (2023)

Among patients treated with statin therapy to guideline-recommended cholesterol levels, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients with higher LDLC levels is uncertain but has implications for the choice of preventive therapies, including bempedoic acid, an agent that reduces both LDLC and hsCRP.
Heart Failure Post-Myocardial Infarction Promotes Mammary Tumor Growth Through the NGF-TRKA Pathway
Authors: Tetsuya Tani, Masayoshi Oikawa, Tomofumi Misaka, Takafumi Ishida, Yasuchika Takeishi
Journal: JACC CardioOncology (2023)

Epidemiological investigations suggest that patients with heart failure have a higher incidence of cancer; however, the causal role of cardiac disease on cancer progression remains unclear. Our study aimed to investigate the impact and underlying mechanisms of myocardial infarction (MI)-induced heart failure on tumor cell growth. We generated a syngeneic mouse model by implanting mammary tumor-derived 4T1 cells into BALB/c mice with MI resulting from ligation of the left anterior descending artery. Mice with MI exhibited increased tumor volume, tumor weight, and Ki67-positive proliferative cells in the tumor tissue compared with the sham-operated mice. Furthermore, RNA-sequencing analysis in the tumor tissue revealed significant enrichment of pathways related to tumor progression, particularly the PI3K-AKT pathway in the MI mice. Upregulation of TRKA phosphorylation, an upstream regulator of PI3K-AKT signaling, was observed in the tumor tissue of the MI mice. We also observed elevated levels of circulating NGF, a ligand of TRKA, and increased NGF expressions in the myocardium after MI. In in vitro experiments, NGF stimulation led to increased cell proliferation, as well as phosphorylation of TRKA and AKT. Notably, inhibition of TRKA by small interfering RNA or the chemical inhibitor GW441756 effectively blocked these effects. Administration of GW441756 resulted in the suppression of tumor volume and cell proliferation in the MI mice. Our study demonstrates that MI promotes mammary tumor growth through the NGF-TRKA pathway. Consequently, inhibiting TRKA could represent a therapeutic strategy for breast cancer patients concurrently experiencing heart failure after MI.
Fostamatinib for warm antibody autoimmune hemolytic anemia: Phase 3, randomized, <scp>double‐blind</scp>, <scp>placebo‐controlled</scp>, global study (<scp>FORWARD</scp>)
Authors: David J. Kuter, Caroline Piatek, Alexander Röth, Asif Siddiqui, Robert P. Numerof, Wolfgang Dummer
Journal: American Journal of Hematology (2023)

Abstract Warm antibody autoimmune hemolytic anemia (wAIHA) is characterized by hemolysis and symptomatic anemia with no approved treatment options. Fostamatinib is an oral spleen tyrosine kinase inhibitor approved in the US and Europe for treatment of adults with chronic immune thrombocytopenia. In this phase 3 study, patients with an insufficient response to ≥1 prior wAIHA treatment were randomized to fostamatinib or placebo. The primary endpoint was the proportion of patients to achieve a durable hemoglobin (Hgb) response (Hgb ≥10 g/dL and increase from baseline of ≥2 g/dL on 3 consecutive visits) during the 24‐week treatment period. Ninety patients were randomized, 45 to each arm. Of the fostamatinib‐treated patients, 35.6% achieved a durable Hgb response versus 26.7% on placebo ( p = .398). A post hoc analysis revealed a large placebo response in Eastern European patients. Significantly more patients on fostamatinib from North America, Australia and Western Europe exhibited a durable Hgb response compared to placebo (36% vs. 10.7%, p = .030). After censoring for Hgb values impacted by steroid rescue received during screening and excluding 2 placebo patients found to likely not have wAIHA, a reanalysis demonstrated a difference in durable Hgb response between fostamatinib and placebo (15/45 [33.3%] vs. 6/43 [14.0%], p = .0395). At least 1 AE was reported in 42 (93.3%) and 40 (88.9%) patients receiving fostamatinib and placebo, respectively. The most common AEs in the fostamatinib group were diarrhea (26.7%), hypertension (24.4%), and fatigue (15.6%). In this study, fostamatinib demonstrated a clinically meaningful benefit for patients in Western regions, and no new safety signals were identified.
Nonischemic or Dual Cardiomyopathy in Patients With Coronary Artery Disease
Authors: Parag Bawaskar, Nicholas Thomas, Khaled Ismail, Yugene Guo, Sanya Chhikara, Pal Satyajit Singh Athwal, Alison Ranum, Achal Jadhav, Abel Hooker Mendez, Ishan Nadkarni, Dominic Frerichs, Pratik Velangi, Tesfatsiyon Ergando, Hassan Akram, Adinan Kanda, Chetan Shenoy
Journal: Circulation (2023)

BACKGROUND: Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from coronary revascularization. Although there are several potential reasons for the lack of benefit, an underexplored possible reason is the presence of coincidental nonischemic cardiomyopathy (NICM). We investigated the prevalence and prognostic significance of NICM in patients with CAD (CAD-NICM). METHODS: We conducted a registry study of consecutive patients with obstructive CAD on coronary angiography who underwent contrast-enhanced cardiovascular magnetic resonance imaging for the assessment of ventricular function and scar at 4 hospitals from 2004 to 2020. We identified the presence and cause of cardiomyopathy using cardiovascular magnetic resonance imaging and coronary angiography data, blinded to clinical outcomes. The primary outcome was a composite of all-cause death or heart failure hospitalization, and secondary outcomes were all-cause death, heart failure hospitalization, and cardiovascular death. RESULTS: Among 3023 patients (median age, 66 years; 76% men), 18.2% had no cardiomyopathy, 64.8% had ischemic cardiomyopathy (CAD+ICM), 9.3% had CAD+NICM, and 7.7% had dual cardiomyopathy (CAD+dualCM), defined as both ICM and NICM. Thus, 16.9% had CAD+NICM or dualCM. During a median follow-up of 4.8 years (interquartile range, 2.9, 7.6), 1116 patients experienced the primary outcome. In Cox multivariable analysis, CAD+NICM or dualCM was independently associated with a higher risk of the primary outcome compared with CAD+ICM (adjusted hazard ratio, 1.23 [95% CI, 1.06–1.43]; P =0.007) after adjustment for potential confounders. The risks of the secondary outcomes of all-cause death and heart failure hospitalization were also higher with CAD+NICM or dualCM (hazard ratio, 1.21 [95% CI, 1.02–1.43]; P =0.032; and hazard ratio, 1.37 [95% CI, 1.11–1.69]; P =0.003, respectively), whereas the risk of cardiovascular death did not differ from that of CAD+ICM (hazard ratio, 1.15 [95% CI, 0.89–1.48]; P =0.28). CONCLUSIONS: In patients with CAD referred for clinical cardiovascular magnetic resonance imaging, NICM or dualCM was identified in 1 of every 6 patients and was associated with worse long-term outcomes compared with ICM. In patients with obstructive CAD, coincidental NICM or dualCM may contribute to the lack of prognostic benefit from coronary revascularization.
The chromatin landscape of the euryarchaeon Haloferax volcanii
Authors: Georgi K. Marinov, S. Tansu Bagdatli, Tong Wu, Chuan He, Anshul Kundaje, William J. Greenleaf
Journal: Genome biology (2023)

Abstract Background Archaea, together with Bacteria, represent the two main divisions of life on Earth, with many of the defining characteristics of the more complex eukaryotes tracing their origin to evolutionary innovations first made in their archaeal ancestors. One of the most notable such features is nucleosomal chromatin, although archaeal histones and chromatin differ significantly from those of eukaryotes, not all archaea possess histones and it is not clear if histones are a main packaging component for all that do. Despite increased interest in archaeal chromatin in recent years, its properties have been little studied using genomic tools. Results Here, we adapt the ATAC-seq assay to archaea and use it to map the accessible landscape of the genome of the euryarchaeote Haloferax volcanii . We integrate the resulting datasets with genome-wide maps of active transcription and single-stranded DNA (ssDNA) and find that while H. volcanii promoters exist in a preferentially accessible state, unlike most eukaryotes, modulation of transcriptional activity is not associated with changes in promoter accessibility. Applying orthogonal single-molecule footprinting methods, we quantify the absolute levels of physical protection of H. volcanii and find that Haloferax chromatin is similarly or only slightly more accessible, in aggregate, than that of eukaryotes. We also evaluate the degree of coordination of transcription within archaeal operons and make the unexpected observation that some CRISPR arrays are associated with highly prevalent ssDNA structures. Conclusions Our results provide the first comprehensive maps of chromatin accessibility and active transcription in Haloferax across conditions and thus a foundation for future functional studies of archaeal chromatin.
Microbes, the ‘silent third partners’ of bee–angiosperm mutualisms
Authors: Shawn A. Steffan, Prarthana S. Dharampal, Jordan G. Kueneman, Alexander Keller, Magda P. Argueta-Guzmán, Quinn S. McFrederick, Stephen L. Buchmann, Rachel L. Vannette, Anna F. Edlund, Celeste C. Mezera, Nolan Amon, Bryan N. Danforth
Journal: Trends in Ecology & Evolution (2023)
VP5-2023: Primary results from BEATcc (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030), a randomised phase III trial of first-line atezolizumab (atezo) combined with a platinum doublet and bevacizumab (bev) for metastatic (stage IVB), persistent or recurrent cervical cancer (R/M CC)
Authors: A. Oaknin, L. Gladieff, J. Martinez-Garcia, G. Villacampa, M. Takekuma, U.F.F. De Giorgi, K. Lindemann, L. Woelber, N. Colombo, L.R. Duska, A. Leary, A. Godoy Ortiz, S. Nishio, A. Angelergues, M.J. Rubio Perez, L. Fariñas Madrid, S. Yamaguchi, D. Lorusso, V. D'Hondt, L. Randall
Journal: Annals of Oncology (2023)